source: Neuromuscular Disorders (NMD)
McDonald CM, Meier T, Voit T, Schara U, Straathof CS, D'Angelo MG, Bernert G, Cuisset JM, Finkel RS, Goemans N, Rummey C, Leinonen M, Spagnolo P, Buyse GM, DELOS Study Group
In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated “by patient” (HR 0.33, p = 0.0187) and for “all BAEs” (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics.
University of California Davis Medical Center, USA; Santhera Pharmaceuticals, Switzerland; Institut de Myologie, France; Universitätsklinikum, Germany; LUMC, The Netherlands; IRCCS Eugenio Medea, Italy; G.v. Preyer'sches Kinderspital, Austria; CHRU de Lille, France; Nemours Children's Hospital, USA; University Hospitals Leuven, Belgium; 4Pharma, Switzerland; Universitäts-Klinikum Freiburg, Germany; Centro Clinico Nemo, Italy; Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Italy; Hospital Universitari i Politècnic La Fe de Valencia, Spain; Astrid Lindgren Children Hospital, Sweden; CHUV, Switzerland; The University of Texas Southwestern Medical Center, USA; The Children's Hospital of Philadelphia, USA; Seattle Children's Hospital, USA
10.1016/j.nmd.2016.05.008 read more
full text source